Author + information
- Nichlas Riise Jespersen,
- Takashi Yokota,
- Kim Nielsen,
- Nicolaj B. Støttrup,
- Jonas Povlsen,
- Flemming Dela and
- Hans Erik Bøtker
Protection against ischemic reperfusion injury is dependent on preserved mitochondrial function and attenuation of reactive oxygen species (ROS). The malate-aspartate shuttle (MAS) connects cytosolic glucose metabolism with mitochondrial oxidation and may constitute a site for regulation of mitochondrial respiration and ROS production. We hypothesized that MAS activity modulates mitochondrial respiration and ROS production, in a similar manner as ischemic preconditioning (IPC) in the post-ischemic reperfused heart and that substrate availability can modulate the cardioprotective effect.
Isolated rat hearts were exposed to 30 min. of global no-flow ischemia followed by 30 min. of reperfusion. Hearts were randomised into: IPC (n=8), pre-ischemic aminooxyacetate (AOA) (0.2 mM, n=8) and control (n=8) perfused with a modified KH-buffer containing 3% bovine serum albumin and glucose (11 mM) or glucose (11 mM) + free fatty acids (palmitate: 0.4 mM). Following reperfusion the left ventricle was rapidly cooled. Cardiac fibers were isolated and permeabilized for measurement of mitochondrial respiration and ROS production by high-resolution respirometry and fluorospectrometry.
IPC but not AOA improved left ventricle developing pressure (LVDP) compared to control (55.1±8.7 and 33.3±7.8 vs. 23.0±6.3 mm Hg; p=0.01 and p=0.32, respectively). IPC and AOA increased mitochondrial respiration compared to control (41.3±2.4 and 41.8±1.7 vs. 30.1±3.1 pmol-s-1-mg-1; p=0.013 and p=0,007, respectively). Mitochondrial ROS production normalized against O2 consumption was attenuated in IPC and AOA vs. control (0.58±0.06 and 0.60±0.04 vs. 1.32±0.12 H2O2/O2; p<0.0001 and p<0.0001, respectively). Additional long chain fatty acid as substrate did not change the results compared to glucose perfused hearts.
IPC and pre-ischemic MAS-inhibition modulate mitochondrial respiration comparably during reperfusion independent of substrate availability. Pre-ischemic MAS-inhibition decreases ROS production during reperfusion and may be involved in the mechanism behind cardioprotection by IPC.
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.-10:45 a.m.
Session Title: Acute Coronary Syndromes: Basic I
Abstract Category: 2. Acute Coronary Syndromes: Basic
Presentation Number: 1127-192
- 2013 American College of Cardiology Foundation